The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts
- PDF / 404,566 Bytes
- 7 Pages / 595.276 x 790.866 pts Page_size
- 65 Downloads / 155 Views
ORIGINAL ARTICLE
The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts Anna Enjuanes • Silvia Ruiz-Gaspa` • Pilar Peris • Dolores Ozalla • ´ lvarez • Andre´s Combalia • M. Jesu´s Martı´nez de Osaba • Luisa A Ana Monegal • Albert Pares • Nuria Guan˜abens
Received: 17 July 2009 / Accepted: 10 November 2009 / Published online: 24 November 2009 Ó Springer Science+Business Media, LLC 2009
Abstract Alendronate is a well-established treatment for osteoporosis and suppresses bone resorption by a direct effect on osteoclasts and their precursors. The effect of alendronate on osteoclasts is produced, at least in part, by the receptor activator of nuclear factor kappaB ligand (RANKL) and the osteoprotegerin (OPG) synthesized by the osteoblasts. This study analyzes the effect of alendronate in cell viability, phosphatase alkaline (ALP) activity and RANKL, and OPG expression in primary human osteoblasts (hOB). Alendronate at concentrations lower than 10-5 M did not have a toxic effect on hOB in vitro and did not modify the ALP activity at least for 72 h. Alendronate did not change OPG expression in basal, 10% FBS, and vitamin D-treated cultures. Similar results were observed at the protein level. Unexpectedly, alendronate at 10-7 and 10-5 M concentrations increased the RANKL expression with the presence of vitamin D in differentiated hOB and
Anna Enjuanes and Silvia Ruiz-Gaspa` have contributed equally to this study. A. Enjuanes (&) S. Ruiz-Gaspa` P. Peris D. Ozalla ´ lvarez A. Combalia M. J. Martı´nez de Osaba L. A A. Monegal N. Guan˜abens Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain e-mail: [email protected] ´ lvarez S. Ruiz-Gaspa` P. Peris L. A M. J. Martı´nez de Osaba A. Pares N. Guan˜abens Centro de Investigaciones Biome´dicas en Red de Enfermedades Hepa´ticas y Digestivas (CIBERehd), Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain A. Pares Liver Unit, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain
this induction of RANKL mRNA levels by alendronate was dose-dependent. However, this effect was not observed in basal and 10% FBS culture conditions. Thus, we conclude that alendronate does not affect the ALP activity and OPG gene expression in differentiated hOB, but may increase RANKL gene expression induced by vitamin D. Keywords Primary human osteoblasts Alendronate RANKL Osteoprotegerin
Introduction Bisphosphonates (BPs) are used in the treatment of osteoporosis and diseases with high bone turnover, as well as in skeletal related events secondary to malignant disease. BPs are stable analogs of pyrophosphate and they are traditionally divided into non-nitrogen-containing (non-N-) and nitrogen-containing (N-) (reviewed in [1, 2]). Non-N-BPs such as etidronate and clodronate suppress bone resorption by incorporating within nonhydrolyzable ATP analogs that have no releasable energy content and lead to osteoclast death. N-BPs such as
Data Loading...
